Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF- II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A- immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs

Identification and characterization of insulin-like growth factor receptors on adult rat cardiac myocytes: linkage to inositol 1,4,5-trisphosphate formation.

Cultured cardiac myocytes from adult Sprague-Dawley rats express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose 6-phosphate (IGF-II/Man6P) receptors and respond to IGF-I with a dose-dependent accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,4-bisphosphate [Ins(1,4)P2]. Specific binding of [125I]IGF-I to isolated membranes from cultured cardiac myocytes amounted to 1-1.2%. Binding of [125I]IGF-I was inhibited by unlabeled IGF-I at nanomolar concentrations and insulin at much higher concentrations. These data suggest that IGF-I binds to its own receptor on rat cardiac myocytes. Competitive binding studies using isolated membranes from cardiac myocytes and [125I]IGF-II showed 2-4% specific binding. Binding of [125I]IGF-II was inhibited by IGF-II and much less potently by IGF-I and insulin. Immunoglobulin G (IgG) 3637 (an IgG directed against the IGF-II/Man6P receptor) partially inhibited binding of [125I]IGF-II whereas nonimmune IgG did not. Affinity cross-linking studies with [125I]IGF-II and cardiac myocyte membranes and subsequent analysis of the ligand-receptor complex using SDS-PAGE and autoradiography showed a radiolabeled band of approximately 250 kilodalton (kDa). The formation of the [125I]IGF-II-receptor complex was inhibited by incubation with IGF-II and IgG 3637 but not by insulin or nonimmune IgG. Western blotting of protein extracts from cultured cardiac myocytes was performed using IgG 3637 and an immunoperoxidase technique for the visualization of the IGF-II/Man6P receptor protein. A specific band at 220 kDa under nonreducing conditions was detected on the blots, providing further evidence for the expression of the IGF-II/Man6P receptor by cardiac myocytes. The effect of IGFs on the accumulation of inositol phosphates was measured by HPLC analysis of perchloric acid extracts from myo-[3H]inositol-labeled cultured cardiac myocytes. IGF-I (50 ng/ml) stimulated the accumulation both of Ins(1,4,5)P3 and Ins(1,4)P2 after 30 sec by 43% and 63%. IGF-II (up to 500 ng/ml) had no significant effect on inositol phosphate accumulation under the same conditions. However, in the presence of millimolar concentrations of Man6P, IGF-II (500 ng/ml) also increased Ins(1,4,5)P3 accumulation by 59%. We conclude that cardiac myocytes from adult rats express IGF receptors and respond to IGFs with the accumulation of Ins(1,4,5)P3 and Ins(1,4)P2. This effect seems to be mediated by an IGF-I receptor-specific pathway

PSMA-targeted therapy for non-prostate cancers

Radioligand therapy (RLT) agents are demonstrating a crucial role in the clinical approach to aggressive malignancies such as metastatic castrate-resistant prostate cancer (m-CRPC). With the recent FDA approval of prostate-specific membrane antigen (PSMA)-targeted RLT for m-CRPC, the field has broadened its gaze to explore other cancers that express PSMA in the tumor parenchyma or tumor neovasculature. In this review article, we discuss current progress in the clinical use of PSMA RLTs in non-prostate cancers such salivary gland cancers, renal cell carcinoma, high grade glioma, and soft tissue sarcoma. We highlight early reports in small case series and clinical trials indicating promise for PSMA-targeted RLT and highlighting the importance of identifying patient cohorts who may most benefit from these interventions. Further study is indicated in non-prostate cancers investigating PSMA RLT dosimetry, PSMA PET/CT imaging as a biomarker, and assessing PSMA RLT safety and efficacy in these cancers

The photon: Experimental emphasis on its wave-particle duality

Two types of Einstein-Podolsky-Rosen experiments were demonstrated recently in our laboratory. It is interesting to see that in an interference experiment (wave-like experiment) the photon exhibits its particle property, and in a beam-splitting experiment (particle-like experiment) the photon exhibits its wave property. The two-photon states are produced from Type 1 and Type 2 optical spontaneous parametric down conversion, respectively

Semi-Phenomenological Analysis of Dynamics of Nonlinear Excitations in One-Dimensional Electron-Phonon System

The structure of moving nonlinear excitations in one-dimensional electron-phonon systems is studied semi-phenomenologically by using an effective action in which the width of the nonlinear excitation is treated as a dynamical variable. The effective action can be derived from Su, Schrieffer and Heeger's model or its continuum version proposed by Takayama, Lin-Liu and Maki with an assumption that the nonlinear excitation moves uniformly without any deformation except the change of its width. The form of the action is essentially the same as that discussed by Bishop and coworkers in studying the dynamics of the soliton in polyacetylene, though some details are different. For the moving excitation with a velocity $v$, the width is determined by minimizing the effective action. A requirement that there must be a minimum in the action as a function of its width provides a maximum velocity. The velocity dependence of the width and energy can be determined. The motions of a soliton in p olyacetylene and an acoustic polaron in polydiacetylene are studied within this formulation. The obtained results are in good agreement with those of numerical simulations.Comment: 19 pages, LaTeX, 7 Postscript figures, to be published in J. Phys. Soc. Jpn. vol.65 (1996) No.

МИРГОРОДСЬКИЙ ПОЛК В РОСІЙСЬКО-ТУРЕЦЬКІЙ ВІЙНІ 1735-1739 РР.

Тема пропонованої шановному читачеві статті знаходиться на перетині воєнної історії та краєзнавства. Після тривалої неуваги, зараз воєнна історія, зокрема козаччини, розробляється досить динамічно. Варто згадати хоча б роботи І.Стороженка [1], В.Заруби [2], О.Сокирка [3], Г.Шпитальова [4]. Одночасно все ще не розроблена докладно воєнна історія полків, які складали Гетьманщину. Хоча спроби такого роду є [5], але вони зосереджені не стільки на воєнній історії, скільки на історії полку загалом і, на жаль, не представлені у вигляді монографічних досліджень та не викладені в Інтернеті, що суттєво ускладнює доступ до результатів таких досліджень. Сюжет, пов’язаний із участю Миргородського полку в російсько-турецькій війні 1735-1739 років, не знайшов висвітлення в історіографії, хоча деякі факти містять дослідження А.Байова [6], О.Апанович [7] та вже згадувана монографія Г.Шпитальова. Протягом війни Миргородський полк брав участь як у далеких виправах, так і в ближніх походах різного роду – фортифікаційних, тривожних, для планової охорони кордонів. Залучення козаків Миргородського полку до далеких походів розпочалося вже у червні 1735 р., коли всі полки (крім Стародубського та Чернігівського) вирушили до фортеці Святого Іоанна на Українській лінії, де мали збиратися для виправи на Крим. До прибуття на лінію генерального осавула Ф.Лисенка обов’язки командира цього з’єднання виконував миргородський полковник Павло Апостол [8]. Кількість козаків Миргородського полку, які вирушили в цей похід, точно невідома. Проте є дані щодо старшини, яка очолила виправу – полковник П.Апостол, суддя Ф.Остроградський, писар В.Тихонович, осавул А.Волевач, хорунжі Т.Калницький та К.Шкурка [9]. Згідно з планами Генеральної військової канцелярії (далі – ГВК) передбачалося для Кримської (1736) виправи мобілізувати 16001 гетьманця, в тому числі 1196 шабель Миргородського полку [10]. Виникли певні проблеми з залученням старшини. Наприклад, миргородський обозний С.Родзянка уперто відмовлявся від походу під приводом хвороби, в яку полковник абсолютно не вірив. Проте С.Родзянка апелював до ГВК, де знайшов підтримку. Врешті, полкова старшина миргородців у цій виправі була представлена тими ж постатями, що й 1735 р., лише осавула А.Волевача замінив його колега С.Ґалаґан [11]. За попередніми планами на 1737 р. Миргородський полк мав виставити 849 шабель у Кримський похід. Після рішення фельдмаршала Мініха залишити слобідських козаків для охорони кордону їм на заміну залучили ще 200 миргородців [12]. На цьому зміни не закінчилися. На вимогу фельдмаршала Мініха Миргородський полк перейшов у його підпорядкування і вирушив замість Кримського в Очаківський похід

Bell State Preparation using Pulsed Non-Degenerate Two-Photon Entanglement

We report a novel Bell state preparation experiment. High-purity Bell states are prepared by using femtosecond pulse pumped \emph{nondegenerate} collinear spontaneous parametric down-conversion. The use of femtosecond pump pulse {\em does not} result in reduction of quantum interference visibility in our scheme in which post-selection of amplitudes and other traditional mechanisms, such as, using thin nonlinear crystals or narrow-band spectral filters are not used. Another distinct feature of this scheme is that the pump, the signal, and the idler wavelengths are all distinguishable, which is very useful for quantum communications.Comment: 4 pages, submitted to PR

On Preparing Entangled Pairs of Polarization Qubits in the Frequency Non-Degenerate Regime

The problems associated with practical implementation of the scheme proposed for preparation of arbitrary states of polarization ququarts based on biphotons are discussed. The influence of frequency dispersion effects are considered, and the necessity of group velocities dispersion compensation in the frequency non-degenerate case even for continuous pumping is demonstrated. A method for this compensation is proposed and implemented experimentally. Physical restrictions on the quality of prepared two-photon states are revealed.Comment: 9 pages, 6 figure